2022
Muresan, Ximena M.; Slabáková, Eva; Procházková, Jiřina; Drápela, Stanislav; Fedr, Radek; Pícková, Markéta; Vacek, Ondřej; Víchová, Ráchel; Suchánková, Tereza; Bouchal, Jan; Kürfürstová, Daniela; Král, Milan; Hulínová, Tereza; Sýkora, Radek P.; Študent, Vladimír; Hejret, Václav; Weerden, Wytske M.; Puhr, Martin; Pustka, Václav; Potěšil, David; Zdráhal, Zbyněk; Culig, Zoran; Souček, Karel
Toll-Like Receptor 3 Overexpression Induces Invasion of Prostate Cancer Cells, whereas Its Activation Triggers Apoptosis. Journal Article
In: The American journal of pathology, vol. 192, no. 9, pp. 1321–1335, 2022, ISSN: 1525-2191 0002-9440, (Place: United States).
Abstract | Links | BibTeX | Tags: *Prostatic Neoplasms/pathology, *Toll-Like Receptor 3/genetics/metabolism, Animals, Apoptosis, Cell Line, Humans, Male, Poly I-C/pharmacology, Prostate/pathology, Tumor
@article{muresan_toll-like_2022,
title = {Toll-Like Receptor 3 Overexpression Induces Invasion of Prostate Cancer Cells, whereas Its Activation Triggers Apoptosis.},
author = {Ximena M. Muresan and Eva Slabáková and Jiřina Procházková and Stanislav Drápela and Radek Fedr and Markéta Pícková and Ondřej Vacek and Ráchel Víchová and Tereza Suchánková and Jan Bouchal and Daniela Kürfürstová and Milan Král and Tereza Hulínová and Radek P. Sýkora and Vladimír Študent and Václav Hejret and Wytske M. Weerden and Martin Puhr and Václav Pustka and David Potěšil and Zbyněk Zdráhal and Zoran Culig and Karel Souček},
doi = {10.1016/j.ajpath.2022.05.009},
issn = {1525-2191 0002-9440},
year = {2022},
date = {2022-09-01},
journal = {The American journal of pathology},
volume = {192},
number = {9},
pages = {1321–1335},
abstract = {Toll-like receptor 3 (TLR3) is an endosomal receptor expressed in several immune and epithelial cells. Recent studies have highlighted its expression also in solid tumors, including prostate cancer (PCa), and have described its role primarily in the proinflammatory response and induction of apoptosis. It is up-regulated in some castration-resistant prostate cancers. However, the role of TLR3 in prostate cancer progression remains largely unknown. The current study experimentally demonstrated that exogenous TLR3 activation in PCa cell lines leads to a significant induction of secretion of the cytokines IL-6, IL-8, and interferon-β, depending on the model and chemoresistance status. Transcriptomic analysis of TLR3-overexpressing cells revealed a functional program that is enriched for genes involved in the regulation of cell motility, migration, and tumor invasiveness. Increased motility, migration, and invasion in TLR3-overexpressing cell line were confirmed by several in vitro assays and using an orthotopic prostate xenograft model in vivo. Furthermore, TLR3-ligand induced apoptosis via cleavage of caspase-3/7 and poly (ADP-ribose) polymerase, predominantly in TLR3-overexpressing cells. These results indicate that TLR3 may be involved in prostate cancer progression and metastasis; however, it might also represent an Achilles heel of PCa, which can be exploited for targeted therapy.},
note = {Place: United States},
keywords = {*Prostatic Neoplasms/pathology, *Toll-Like Receptor 3/genetics/metabolism, Animals, Apoptosis, Cell Line, Humans, Male, Poly I-C/pharmacology, Prostate/pathology, Tumor},
pubstate = {published},
tppubtype = {article}
}
Toll-like receptor 3 (TLR3) is an endosomal receptor expressed in several immune and epithelial cells. Recent studies have highlighted its expression also in solid tumors, including prostate cancer (PCa), and have described its role primarily in the proinflammatory response and induction of apoptosis. It is up-regulated in some castration-resistant prostate cancers. However, the role of TLR3 in prostate cancer progression remains largely unknown. The current study experimentally demonstrated that exogenous TLR3 activation in PCa cell lines leads to a significant induction of secretion of the cytokines IL-6, IL-8, and interferon-β, depending on the model and chemoresistance status. Transcriptomic analysis of TLR3-overexpressing cells revealed a functional program that is enriched for genes involved in the regulation of cell motility, migration, and tumor invasiveness. Increased motility, migration, and invasion in TLR3-overexpressing cell line were confirmed by several in vitro assays and using an orthotopic prostate xenograft model in vivo. Furthermore, TLR3-ligand induced apoptosis via cleavage of caspase-3/7 and poly (ADP-ribose) polymerase, predominantly in TLR3-overexpressing cells. These results indicate that TLR3 may be involved in prostate cancer progression and metastasis; however, it might also represent an Achilles heel of PCa, which can be exploited for targeted therapy.